Blood plasma contains several protens that exhibit insulin-like effects when tested in isolated tissue systems or when injected into animals. These insulin-like proteins are collectively termed "nonsuppressible" since addition of insulin antibody to the test system fails to suppress their biological activity. Included in this group of interesting proteins are the somatomedins, insulin-like growth factors I and II, and a much larger molecular weight protein presently termed nonsuppressible insulin-like protein (NSILP). Most investigators now agree that NSILP comprises 60-90% of the total nonsuppressible insulin-like activity in plasma; however, the physiological role of NSILP and its relationship to other insulin-like growth factors remains unclear. The objectives of this proposal are to revise purification procedures for NSILP, to obtain unambiguous information on its primary structure, to define the hormonal control for its production by the liver, and to clarify its role in metabolic fuel homeostasis and tissue growth processes. A recently developed immunoassay for NSILP will provide the basic tool facilitating the design and execution of these studies. The significance of this research extends into several related areas of investigation concerned with hormonal control of the disposition of metabolic fuels in animals and with the regulation of tissue growth and repair processes.